2 Boston patients had transplants of marrow, halted powerful drugs
Steve Forrest/International AIDS/file
Boston researchers are reporting the return of the HIV virus in two patients who had become virus-free after undergoing bone marrow transplants, dashing hopes of a possible cure that had generated widespread excitement.
The rebound of the virus shows its persistence, and that it can hide in places in the body where it’s hard to find, said the lead scientist, Dr. Timothy Henrich of Brigham and Women’s Hospital. But he said the team has gleaned significant clues from the cases for designing next-generation treatments to battle the virus, which causes AIDS.
Henrich, who presented the preliminary findings Thursday at an international conference of AIDS researchers in Florida, said doctors pinpointed signs of the virus in both patients, who had beaten back the infections to undetectable levels earlier this year. The patients underwent bone marrow transplants several years ago for cancer, and had since stopped their powerful antiretroviral medications, which are typically given to those infected with the virus to keep it in check.
Other researchers who heard the presentation said the results were disappointing but the Boston team’s approach and data will dramatically advance strategies for battling HIV.
Henrich, a Brigham infectious diseases associate physician, said in an interview that the researchers decided to release their initial findings, before analyzing all the results, so others in the field could know as soon as possible. Other scientists were designing similar studies, with HIV patients who had bone marrow transplants, based on the earlier Boston findings.
“We felt it would be scientifically unfair to not let people know how things are going, especially for potential patients,” Henrich said.
The two patients in the Boston study had battled HIV for years. They agreed to stop taking their HIV medications earlier this year to test whether the medicine was holding the infections in check, or whether it was the transplant of healthy donor bone marrow cells each received that was vanquishing signs of the virus in their bodies. Both had received the transplants after chemotherapy and other treatments had failed to stop their Hodgkin’s lymphoma, a cancer of the blood.
For weeks, Henrich’s team carefully tested the patients’ blood, searching for signs of HIV. In July, with one patient off the HIV medications for seven weeks, and the other patient off for 15, the scientists reported their early, encouraging results: They could find no trace of the virus in their blood cells.
But in August, the scientists detected HIV in one of the patients, who then resumed taking medication. The other remained seemingly HIV-free. Concerned about the ethics of continuing the study, the scientists gave the patient the choice of going back on the drugs. The patient opted to stay off the medicine.
Last month, after eight months with no HIV detected, signs of the virus reemerged and the patient went back on medication, too.
Henrich said the reemergence of the virus demonstrates that HIV reservoirs — latent cells that carry the genetic code of HIV — are lurking deeper in the body and are more persistent than scientists had realized.
“This suggests that we need to look deeper, or we need to be looking in other tissues . . . the liver, gut, and brain,” Henrich said. “These are all potential sources, but it’s very difficult to obtain tissue from these places so we don’t do that routinely.”
To date, there is only one patient believed to have been cured of HIV. German doctors in 2009 reported that an American, Timothy Ray Brown, was given a bone marrow transplant for leukemia and appeared to have been cured of HIV as well.
Brown, known as the “Berlin patient,” received bone marrow from a donor who carried a rare gene mutation, CCR5-delta32, which is thought to provide resistance to HIV. Previously, researchers had not observed similar results with ordinary donor marrow, such as those cells given to the Boston patients.
In preparation for his transplant, Brown also received massive doses of harsh chemotherapy and radiation treatments to knock out the HIV infection, an extreme approach not practical for widespread use, said Dr. Steven Deeks, an HIV researcher and professor of medicine at the University of California, San Francisco. The Boston patients received much lower doses before their transplants.
“There are a lot of hurdles,” said Deeks, who was at the Florida meeting. “But this [the Boston researchers’ approach] dramatically advanced the cure research agenda.”
Henrich and other researchers say bone marrow transplants, which are risky and can be lethal, are not a practical or ethical approach to treating HIV, especially in patients who do not have cancer.
But the Boston findings help researchers better understand how and where HIV persists in the body, potentially helping them design treatments that may be more precise in eradicating the virus.
“This is certainly telling us a lot about persistence, what we need to do, and how low we need to drop the levels of HIV reservoirs in order to allow patients to achieve remission,” Dr. Katherine Luzuriaga, professor of molecular medicine, pediatrics and medicine at UMass Medical School, said by phone from the conference.
Luzuriaga and colleagues recently reported that a 3-year old, who was born with HIV and given antiretroviral drugs within 30 hours of birth, remains in remission despite being off medications for 18 months.
Henrich’s team is now scouring its data to figure out why one patient was able to fend off the virus’s return months longer than the other patient they studied. Among the factors they are scrutinizing are the age when each was infected with HIV, the manner of infection, and the levels of virus in each patient before they underwent bone marrow transplantation.
The team also plans to widen its study, enroll more HIV-infected patients who have had bone marrow transplants, and search for signs of infections in additional tissue before stopping HIV medications. Among the questions the researchers hope to answer is whether the timing of when HIV medication is halted may play a role in its reemergence.
“We go back to the drawing board,” Henrich said. “It’s exciting science, even if it’s not the outcome we would have liked.”
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